This invention relates generally to chromatography systems and more specifically to liquid chromatography systems, particularly those in which so-called gradient elution techniques are employed.
In the course of carrying out liquid chromatography methods, particularly where high-pressure liquid chromatography is practiced with relatively large reservoirs (e.g., in excess of about 10 ml), it is found that the time constant incident to reattainment of equilibrium following a sudden pressure change in the system, can be of the order of several minutes, e.g., typically 1 to 6 minutes. The sudden pressure change noted can arise e.g., in consequence of a programmed change in flow rate, or in consequence of practicing gradient elution techniques, i.e., the use of a solvent mixture with continuously changing concentration ratio -- where the source of the pressure change phenomenon is the variation in viscosity with change in relative concentration of the components. These oscillatory effects are all driven by the expansion and compression of the solvents in the reservoir or reservoirs, i.e., the oscillatory effects are ultimately caused by the fact that the solvents, although not always so though of, are indeed slightly compressible.
The normal and usual arrangement in chromatography apparatus of the type considered herein entails use of one or more reservoirs, which are basically in the nature of syringe pumps. A given reservoir thus may comprise a cylindrical tube or the like, having a volume V. A piston of circular cross-section is mounted for axially directed movement in the cylinder, and is normally driven by motor means at a velocity v, which is constant over a given time interval to provide a constant average flow rate Q.sub.o for the liquid mobile phase present within the reservoir. Assuming, however, that for the reasons mentioned above a sudden pressure change is effected, the compressibility k of the liquid causes a transient change from the average flow rate Q.sub.o for the liquid phase flowing out of the reservoir, the transient flow rate Q.sub.t of the flow being in accordance with the equation: EQU Q.sub.t = (-KV) (dP/dt), (1)
where k is the fluid compressibility, V is the reservoir volume, and dP/dt is the time derivative of pressure in the reservoir. It can be seen from equation (1) that a sudden increase or decrease in P cause the volume of the liquid phase to transiently contract or expand, due to the compressibility of the liquid phase thereby causing the transient change in the flow rate.
The net effect of the foregoing phenomena is one of providing erroneous concentration variations at the output of the fluid mixer. These concentrations variations can interact with the chromatographic column to produce additional pressure changes which reinforce the initial pressure disturbance, thereby generating a continuing instability or oscillation.
In accordance with the foregoing, it may be regarded as an object of the present invention to provide method and apparatus for use with liquid chromatography systems, which reduce the effectivetime constant incident to reattainment of equilibrium pressure and flow, and thereby damp the oscillatory behavior following a change in fluid pressure of the system.